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Younossi Z.,Center for Liver Diseases | Younossi Z.,Health Integrated | Henry L.,Center for Outcomes Research in Liver Diseases
Gastroenterology | Year: 2016

Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are common causes of chronic liver disease. NAFLD is associated with obesity and metabolic syndrome whereas ALD is associated with excessive alcohol consumption. Both diseases can progress to cirrhosis, hepatocellular carcinoma, and liver-related death. A higher proportion of patients with NAFLD die from cardiovascular disorders than patients with ALD, whereas a higher proportion of patients with ALD die from liver disease. NAFLD and ALD each are associated with significant morbidity, impairment to health-related quality of life, and economic costs to society. © 2016 AGA Institute.


Ratziu V.,University Pierre and Marie Curie | Goodman Z.,Center for Liver Diseases | Sanyal A.,Virginia Commonwealth University
Journal of Hepatology | Year: 2015

Of all the aspects of non-alcoholic fatty liver disease (NAFLD), the slowest advances have occurred in the therapeutic field. Thirty-five years after its formal description and after 15 years of intense scrutiny from researchers worldwide, there is still no approved drug for the treatment of non-alcoholic steatohepatits (NASH). In the meantime, progress in the understanding of pathophysiology, diagnosis - both invasive and non-invasive, epidemiology and even natural history have been substantial or, at times, spectacular. In contrast, hepatitis C virus (HCV) therapy underwent constant improvement and even before the great acceleration of the past few years, patients were already being offered approved therapies that were increasingly more efficient. What then explains such a slow pace of therapeutic advances in NASH, and will this change in the near future? Here we will review commonly-held myths that have diverted attention from therapy of NASH, obstacles that have slowed down industrial development of drugs for this indication, and recent achievements that will create better conditions for drug development programs. We will also briefly review current knowledge of non-pharmacological and pharmacological management in this early era of NASH therapies. © 2015 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.


Brown A.,Imperial College London | Goodman Z.,Center for Liver Diseases
Expert Review of Gastroenterology and Hepatology | Year: 2012

Hepatitis B virus (HBV) infection currently accounts for approximately 600,000 deaths per year resulting from progression of liver fibrosis to cirrhosis and hepatocellular carcinoma. Treatment of chronic hepatitis B with antiviral agents aims to improve survival through the reduction of HBV DNA to undetectable levels and the resultant prevention of disease progression. In recent years, observations in various disease areas have shown that liver fibrosis can be reversed if the underlying cause of the liver damage is effectively addressed. In line with these observations, there is now considerable evidence to suggest that effective sustained suppression of HBV replication with long-term anti-HBV treatment can result in measurable improvements in liver fibrosis over time, even in patients with advanced cirrhosis. This review article provides an overview of currently available data on regression of fibrosis and cirrhosis in patients with chronic hepatitis B treated with nucleoside and nucleotide analog inhibitors of HBV. © 2012 Expert Reviews Ltd.


Younossi Z.,Center for Liver Diseases | Henry L.,Health Integrated
Alimentary Pharmacology and Therapeutics | Year: 2015

Background Treatment for chronic hepatitis C (CH-C) is rapidly changing and moving away from an interferon and ribavirin-based therapy to interferon-free ribavirin-free all oral regimens. These regimens are simpler and shorter to administer with very high efficacy rates and better side effect profiles. As advances in the treatment of CH-C occur, it is imperative to capture both clinical outcomes (efficacy and safety) as well as patient-reported outcomes (PROs). In fact, PROs assesses and quantifies the impact of these regimens on patient experience. PROs assess patients' health-related quality of life (HRQOL) especially in the realms of fatigue and neuropsychiatric issues such as depression which can affect treatment adherence and work productivity. Aim To review the literature related to PRO's in HCV patients and summarise the impact of CH-C and its treatment on PROs. Methods Databases Ovid MEDLINE and PubMed were searched from 1990 to October 2014 using a combination of MEsh, thesaurus terms and relevant text words: hepatitis C, CH-C, treatment, quality of life, health-related quality of life, fatigue, work productivity, adherence, patient-reported outcomes, direct acting anti-viral agents and second generation direct acting anti-viral agents. Each manuscript was assessed for pertinence to the issue of PROs in CH-C as well as the quality of study design and publications. Results From the literature, it is evident that CH-C patients have baseline PRO impairment. Furthermore, treatment with interferon with or without ribavirin and first generation DAAs causes additional PRO burden which can negatively impact treatment adherence and indirectly, treatment efficacy and work productivity. The new treatment regimens with interferon- and ribavirin-free regimens not only have very high efficacy, but also result in the improvement of PRO scores as early as 2 weeks into treatment as well as possibly better adherence to treatment regimens. Conclusions CH-C and its treatment have been associated with patient-reported outcome impairment. The new IF-free and RBV-free regimens are associated with high efficacy and substantial improvement of patient-reported outcomes in clinical trial setting. Although very encouraging, more data are needed to assess patient-reported outcomes, adherence and work productivity of CH-C patients in the real world setting of clinical practice. © 2015 John Wiley & Sons Ltd.


Goodman Z.D.,Center for Liver Diseases
Clinics in Liver Disease | Year: 2014

Obesity and insulin resistance produce alterations in the liver's normal role in lipid metabolism resulting in a sequence of changes recognizable on liver biopsy. Hepatocellular fat vacuoles increase with BMI, producing steatosis. Steatohepatitis occurs when there is also cytoskeletal damage with loss of keratin filaments, ballooning of affected liver cells and formation of Mallory-Denk bodies. Activation of hepatic stellate cells produces fibrosis in the perisinusoidal spaces. With continuing fibrogenesis there is progression to bridging fibrosis and cirrhosis. Hepatocellular carcinoma may develop in the cirrhotic liver, but both hepatocellular adenoma and hepatocellular carcinoma may occur in pre-cirrhotic fatty liver disease. © 2014 Elsevier Inc.

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